TCTN1 p.Ser109Ser

Variant names:

• chr12-110619939-C-C
• ENST00000397659.9:c.

Your query was ambiguous. Multiple possible variants found:

• chr12-110619940--
• chr12-110619942-A-T
• chr12-110619942-A-C
• chr12-110619942-A-G
• chr12-110619940-TCA-AGT
• chr12-110619940-TCA-AGC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000397659.9(TCTN1):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TCTN1 ENST00000397659.9 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.48
• Publications: 0 publications found

Genes affected

TCTN1 (HGNC:26113): (tectonic family member 1) This gene encodes a member of a family of secreted and transmembrane proteins. The orthologous gene in mouse functions downstream of smoothened and rab23 to modulate hedgehog signal transduction. This protein is a component of the tectonic-like complex, which forms a barrier between the ciliary axoneme and the basal body. A mutation in this gene was found in a family with Joubert syndrome-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

TCTN1 Gene-Disease associations (from GenCC):

• Joubert syndrome 13

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397659.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCTN1	ENST00000397659.9	TSL:1 MANE Select	c.		exon_region	Exon 2 of 15	ENSP00000380779.4	Q2MV58-2
	TCTN1	ENST00000551590.5	TSL:1	c.		exon_region	Exon 2 of 15	ENSP00000448735.1	Q2MV58-1
	TCTN1	ENST00000397655.7	TSL:1	c.		exon_region	Exon 2 of 15	ENSP00000380775.3	Q2MV58-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-111057744;